The overall objective of this project is to develop potent, selective, and bioactive small molecule modulators of Wip1 for use as chemical probes and starting points for therapeutic development. During this period, the project team developed and validated a Wip1 activity assay amenable for high-throughput screening. The Wip1 activity assay was validated by quantitative high-throughput screening of the NCATS pharmaceutical collection. The validated assay is being used for high-throughput screening of the entire NCATS collection of small molecules. Other cell-based activity assays have also been optimized and validated. Additional efforts have focused on detailed mechanistic studies of the enzymes mechanism of action, which could be exploited during medicinal chemistry optimization of chemical leads.